Virulence of Pseudomonas aeruginosa exposed to carvacrol: alterations of the Quorum sensing at enzymatic and gene levels.

The main goal of this study was to evaluate the inhibition of Pseudomonas aeruginosa virulence factors and Quorum Sensing during exposure to carvacrol. P. aeruginosa (ATCC 10154) was exposed to carvacrol determining changes in biofilm development, motility, acyl-homoserine lactones (AHL) synthesis and relative expression of lasI/lasR. Docking analysis was used to determinate interactions between carvacrol with LasI and LasR proteins. P. aeruginosa produced 60% lower AHLs when exposed to carvacrol (1.9 mM) compared to control, without affecting cellular viability, indicating a reduction on the LasI synthase activity. AHL-C12, C6, and C4 were detected and related to biofilm development, motility, and pyocyanin production, respectively. The presence of carvacrol reduced the expression of lasR, without affecting lasI gen. Moreover, computational docking showed interactions of carvacrol with amino acids in the active site pocket of LasI (-5.6 kcal mol-1) and within the binding pocket of LasR (-6.7 kcal mol-1) of P. aeruginosa. These results demonstrated that virulence of P. aeruginosa was reduced by carvacrol, by inhibiting LasI activity with the concomitant reduction on the expression of lasR, biofilm and swarming motility. This study provides relevant information about the effect of carvacrol against quorum sensing to inhibit virulence factors of P. aeruginosa at enzymatic and gene levels. These findings can contribute to the development of natural anti-QS products, which can affect pathogenesis.